title: Increased expression of complement regulators CD55 and CD59 on peripheral blood cells in patients with EAHEC O104:H4 infection.
abstract: BACKGROUND
  An outbreak of Shiga Toxin 2 (Stx-2) producing enterohemorrhagic and enteroaggregative E.coli (EAHEC) O104H4 infection in May 2011 caused enterocolitis and an unprecedented high 22% rate of hemolytic uremic syndrome (HUS). The monoclonal anti-C5 antibody Eculizumab (ECU) has been used experimentally in EAHEC patients with HUS but treatment efficacy is uncertain. ECU can effectively prevent hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) caused by a lack of complement-regulating CD55 and CD59 on blood cells. We hypothesized a low expression of CD55 and CD59, as seen in PNH, might correlate with HUS development in EAHEC patients.
  
  
  METHODS
  76 EAHEC patients (34 only gastrointestinal symptoms [GI], 23: HUS, 19: HUS and neurological symptoms [HUS/N]) and 12 healthy controls (HC) were tested for the expression of CD55 and CD59 on erythrocytes and leukocytes retrospectively. Additionally, the effect of Stx-2 on CD55 and CD59 expression on erythrocytes and leukocytes was studied ex vivo.
  
  
  RESULTS
  CD55 expression on erythrocytes was similar in all patient groups and HC while CD59 showed a significantly higher expression in HUS and HUS/N patients compared to HC and the GI group. CD55 and CD59 expression on leukocytes and their subsets was significantly higher in all patient groups compared to HC regardless of treatment type. However, CD59 expression on erythrocytes was significantly higher in HUS and HUS/N patients treated combined with plasma separation (PS) and ECU compared to HC. Adding Stx-2 ex vivo had no effect on CD55 and CD59 expression on leukocytes from HC or patients.
  
  
  CONCLUSIONS
  HUS evolved independently from CD55 and CD59 expression on peripheral blood cells in EAHEC O104:H4 infected patients. Our data do not support a role for CD55 and CD59 in HUS development during EAHEC O104:H4 infection and point to a different mechanism within the complement system for HUS development in EAHEC patients.
authors.affiliation: Department of Medicine, University Medical Center Eppendorf, Hamburg, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Dammermann
authors.forename: Pim
authors.initials: P
authors.lastname: Schipper
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ullrich
authors.forename: Katharina
authors.initials: K
authors.lastname: Fraedrich
authors.forename: Julian
authors.initials: J
authors.lastname: Schulze Zur Wiesch
authors.forename: Thorben
authors.initials: T
authors.lastname: Fründt
authors.forename: Gisa
authors.initials: G
authors.lastname: Tiegs
authors.forename: Ansgar
authors.initials: A
authors.lastname: Lohse
authors.forename: Stefan
authors.initials: S
authors.lastname: Lüth
mesh_terms: D000328:Adult; D001773:Blood Cells / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D018958:CD55 Antigens / Q000097:blood*; D018957:CD59 Antigens / Q000097:blood*; D003165:Complement System Proteins / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D054324:Enterohemorrhagic Escherichia coli / Q000502:physiology*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D022641:Shiga Toxin 2 / Q000378:metabolism; D014508:Urea / Q000097:blood
chemical_list: D018958:CD55 Antigens; D018957:CD59 Antigens; D006454:Hemoglobins; D022641:Shiga Toxin 2; D014508:Urea; D003165:Complement System Proteins; D003404:Creatinine